PDF(Pubmed)
Abstract：
Recently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC). However, patients show highly heterogeneous responses to treatment, and predictive biomarkers are lacking. We performed a systematic review and meta-analysis to assess the potential of PD-L1 expression as a biomarker for treatment response and survival in patients with BTC undergoing anti-PD-1/PD-L1 therapy.
We conducted a comprehensive systematic literature search through June 2023, utilizing the PubMed, EMBASE, and Cochrane Library databases. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) according to PD-L1 expression. Subgroup analyses and meta-regression were performed to identify possible sources of heterogeneity.
A total of 30 studies was included in the final analysis. Pooled analysis showed no significant differences in ORR (odds ratio [OR], 1.56; 95% confidence intervals [CIs], 0.94-2.56) and DCR (OR, 1.84; 95% CIs, 0.88-3.82) between PD-L1 (+) and PD-L1 (-) patients. In contrast, survival analysis showed improved PFS (hazard ratio [HR], 0.54, 95% CIs, 0.41-0.71) and OS (HR, 0.58; 95% CI, 0.47-0.72) among PD-L1 (+) patients compared to PD-L1 (-) patients. Sensitivity analysis excluding retrospective studies showed no significant differences with the primary results. Furthermore, meta-regression demonstrated that drug target (PD-1 vs. PD-L1), presence of additional intervention (monotherapy vs. combination therapy), and PD-L1 cut-off level (1% vs. ≥5%) significantly affected the predictive value of PD-L1 expression.
PD-L1 expression might be a helpful biomarker for predicting PFS and OS in patients with BTC undergoing anti-PD-1/PD-L1 therapy. The predictive value of PD-L1 expression can be significantly influenced by diagnostic or treatment variables.
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023434114.
We conducted a comprehensive systematic literature search through June 2023, utilizing the PubMed, EMBASE, and Cochrane Library databases. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) according to PD-L1 expression. Subgroup analyses and meta-regression were performed to identify possible sources of heterogeneity.
A total of 30 studies was included in the final analysis. Pooled analysis showed no significant differences in ORR (odds ratio [OR], 1.56; 95% confidence intervals [CIs], 0.94-2.56) and DCR (OR, 1.84; 95% CIs, 0.88-3.82) between PD-L1 (+) and PD-L1 (-) patients. In contrast, survival analysis showed improved PFS (hazard ratio [HR], 0.54, 95% CIs, 0.41-0.71) and OS (HR, 0.58; 95% CI, 0.47-0.72) among PD-L1 (+) patients compared to PD-L1 (-) patients. Sensitivity analysis excluding retrospective studies showed no significant differences with the primary results. Furthermore, meta-regression demonstrated that drug target (PD-1 vs. PD-L1), presence of additional intervention (monotherapy vs. combination therapy), and PD-L1 cut-off level (1% vs. ≥5%) significantly affected the predictive value of PD-L1 expression.
PD-L1 expression might be a helpful biomarker for predicting PFS and OS in patients with BTC undergoing anti-PD-1/PD-L1 therapy. The predictive value of PD-L1 expression can be significantly influenced by diagnostic or treatment variables.
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023434114.
摘要：
■最近，抗程序性细胞死亡蛋白1(PD-1)/程序性死亡配体1(PD-L1)免疫治疗为晚期胆道癌(BTC)提供了有希望的结果.然而,患者对治疗表现出高度异质性的反应，缺乏预测性生物标志物。我们进行了系统评价和荟萃分析，以评估PD-L1表达作为接受抗PD-1/PD-L1治疗的BTC患者治疗反应和生存的生物标志物的潜力。
■我们利用PubMed进行了全面系统的文献检索，直到2023年6月，EMBASE,和Cochrane图书馆数据库。感兴趣的结果包括客观反应率(ORR)，疾病控制率（DCR），无进展生存期（PFS），和总生存期（OS）根据PD-L1表达。进行亚组分析和荟萃回归以确定异质性的可能来源。
■共有30项研究纳入最终分析。汇总分析显示ORR没有显著差异(比值比[OR]，1.56；95%置信区间[CI]，0.94-2.56)和DCR(或，1.84；95%CIs，PD-L1（+）和PD-L1（-）患者之间的0.88-3.82）。相比之下,生存分析显示PFS改善(风险比[HR]，0.54，95%CI，0.41-0.71）和OS（HR，与PD-L1（-）患者相比，PD-L1（+）患者为0.58；95%CI，0.47-0.72）。不包括回顾性研究的敏感性分析显示与主要结果没有显着差异。此外，荟萃回归表明，药物靶标(PD-1vs.PD-L1),存在额外的干预(单一疗法与联合治疗)，和PD-L1截止水平(1%与≥5%)显著影响PD-L1表达的预测价值。
■PD-L1表达可能是预测接受抗PD-1/PD-L1治疗的BTC患者PFS和OS的有用生物标志物。PD-L1表达的预测值可显著受到诊断或治疗变量的影响。
■https://www.crd.约克。AC.英国/PROSPERO,标识符CRD42023434114。
■我们利用PubMed进行了全面系统的文献检索，直到2023年6月，EMBASE,和Cochrane图书馆数据库。感兴趣的结果包括客观反应率(ORR)，疾病控制率（DCR），无进展生存期（PFS），和总生存期（OS）根据PD-L1表达。进行亚组分析和荟萃回归以确定异质性的可能来源。
■共有30项研究纳入最终分析。汇总分析显示ORR没有显著差异(比值比[OR]，1.56；95%置信区间[CI]，0.94-2.56)和DCR(或，1.84；95%CIs，PD-L1（+）和PD-L1（-）患者之间的0.88-3.82）。相比之下,生存分析显示PFS改善(风险比[HR]，0.54，95%CI，0.41-0.71）和OS（HR，与PD-L1（-）患者相比，PD-L1（+）患者为0.58；95%CI，0.47-0.72）。不包括回顾性研究的敏感性分析显示与主要结果没有显着差异。此外，荟萃回归表明，药物靶标(PD-1vs.PD-L1),存在额外的干预(单一疗法与联合治疗)，和PD-L1截止水平(1%与≥5%)显著影响PD-L1表达的预测价值。
■PD-L1表达可能是预测接受抗PD-1/PD-L1治疗的BTC患者PFS和OS的有用生物标志物。PD-L1表达的预测值可显著受到诊断或治疗变量的影响。
■https://www.crd.约克。AC.英国/PROSPERO,标识符CRD42023434114。
